ATP-sensitive potassium channels (K-ATP) in retina: a key role for delayedischemic tolerance

The objectives of the present study were to determine the localization of K -ATP channels in normal retina and to evaluate their potential roles in isc hemic preconditioning (IPC) in a rat model of ischemia induced by increased intraocular pressure (IOP). Brown Norway rats were subjected to sublethal 3-, lethal 20- and 40-min ischemia and the functional recovery was evaluate d using electroretinography. The time interval between ischemic insults ran ged from 1 to 72 h. The effects of K-ATP channel blockade on IPC protection were studied by treatment with 0.01% glipizide. IPC was mimicked by inject ion of K-ATP channel openers of 0.01% (-)cromakalim or 0.01% P1060 72 h bef ore 20-min ischemia. Co-expression of K-ATP, channel subunits Kir6.2/SUR1 w as observed in the retinal pigment epithelium, inner segments of photorecep tors, outer plexiform and ganglion cell layers and at the border of the inn er nuclear layer. In contrast to a 20- or 40-min ischemia, a 3-min ischemia induced no alteration of the electroretinogram (ERG) and constituted the p reconditioning stimulus. An ischemic challenge of 40 min in preconditioned rats induced impairment of retinal function. However, animals preconditione d 24, 48 and 72 h before 20-min ischemia had a significant improvement of t he ERG. (-)Cromakalim and P1060 mimicked the effect of IPC. Glipizide signi ficantly suppressed the protective effects of preconditioning. In conclusio n, activation of K-ATP channels plays an important role in the mechanism of preconditioning by enhancing the resistance of the retina against a severe ischemic insult. (C) 2001 Elsevier Science B.V. All rights reserved.